We have documented that chlordane, a chlorinated hydrocarbon insecticide, is immunotoxic to mice exposed in utero, a documented route of exposure in man. Mice exposed to chlordane manifested a depression of cell-mediated immunity (CMI) for essentially life, while no apparent effect was obsered in terms of T-cell-dependent humoral immunity. In the proposed studies, we will assess the effect of in utero exposure to chlordane on host resistance to two important human viral pathogens, influenza type A virus and herpes simplex virus, type 1. These viruses were chosen because they induce primary infections which require a functionally intact CMI system for resolution. Inintially, we will determine the effect of chlordane on host resistance by comparative quantal infectivity titrations of stock virus preparations. The effect of chlordane will be further studied by an assessment of the kinetics of viral replication in target organs using coventional infectivity assays, by a determination of the temporal distribution and quality of intracellular viral antigens in selected tissues by immunofluorescence assay and by quantification of interferon activity in selected tissues using a bioassay procedure. Cell-mediated cytotoxicity and antibody-dependent cellular cytotoxocity assays will be performed to define the chlordane-induced deficit in CMI as it relates to antiviral host resistance. The kinetics of the antibody response will also be determined. Sera will be assayed for viral neutralizing antibody by plaque reduction assay and for immunoglobulin and subclass specific antiviral antibody by the indirect enzyme-linked immunosorbent (ELISA) assay to determine whether a selective chlordane-induced depression occurs in antiviral antibody synthesis. In the case of influenze, lung lavage fluids will also be assayed for antibody using the inderect ELISA assay. Histopathological studies will be performed to correlate virological and immunological findings. Lastly, we will determine the effect of exposure to cholordane on IgE antibody syntesis as it may relate to induction of an allergic phenotype.